Novel small molecule epithelial sodium channel inhibitors as potential therapeutics in cystic fibrosis – a patent evaluation

Bibliography

• Canessa CM, Schild L, Buell G, et al. Amiloride-sensitive epithelial Na+ channel is made of three homologous subunits. Nature 1994;367(6462):463-7
   PubMed Web of Science ®Google Scholar
• Jasti J, Furukawa H, Gonzales EB, et al. Structure of acid-sensing ion channel 1 at 1.9 A resolution and low pH. Nature 2007;449(7160):316-23
   PubMed Web of Science ®Google Scholar
• Waldmann R, Champigny G, Bassilana F, et al. Molecular cloning and functional expression of a novel amiloride-sensitive Na+ channel. J Biol Chem 1995;270(46):27411-14
   PubMed Web of Science ®Google Scholar
• Wesch D, Miranda P, Afonso-Oramas D, et al. The neuronal-specific SGK1.1 kinase regulates {delta}-epithelial Na+ channel independently of PY motifs and couples it to phospholipase C signaling. Am J Physiol Cell Physiol 2010;299(4):C779-90
   Web of Science ®Google Scholar
• Wesch D, Althaus M, Miranda P, et al. Differential N-termini in epithelial Na+ channel delta subunit isoforms modulate channel trafficking to the membrane. Am J Physiol Cell Physiol 2011
   PubMed Web of Science ®Google Scholar
• Giraldez T, Rojas P, Jou J, et al. The epithelial sodium channel delta-subunit: new notes for an old song. Am J Physiol Renal Physiol 2012;303(3):F328-38
   Web of Science ®Google Scholar
• Giraldez T, Domínguez J, Alvarez de La Rosa D. ENaC in the brain-future perspectives and pharmacological implications. Curr Mol Pharmacol 2013;6(1):44-9
   PubMedGoogle Scholar
• Koefoed-Johnsen V, Ussing HH. The nature of the frog skin potential. Acta Physiol Scand 1958;42(3-4):298-308
   PubMedGoogle Scholar
• Fronius M, Clauss WG, Althaus M. Why do we have to move fluid to be able to breathe? Front Physiol 2012;3:146
   PubMed Web of Science ®Google Scholar
• Knowles MR, Boucher RC. Mucus clearance as a primary innate defense mechanism for mammalian airways. J Clin Invest 2002;109(5):571-7
   PubMed Web of Science ®Google Scholar
• Button B, Cai L, Ehre C, et al. A periciliary brush promotes the lung health by separating the mucus layer from airway epithelia. Science 2012;337(6097):937-41
   PubMed Web of Science ®Google Scholar
• Boucher RC. New concepts of the pathogenesis of cystic fibrosis lung disease. Eur Respir J 2004;23(1):146-58
   PubMed Web of Science ®Google Scholar
• Dickey BF. Biochemistry. Walking on solid ground. Science 2012;337(6097):924-5
   PubMed Web of Science ®Google Scholar
• Althaus M. ENaC inhibitors and airway re-hydration in cystic fibrosis: state of the art. Curr Mol Pharmacol 2013;6(1):3-12
   PubMedGoogle Scholar
• Chang SS, Grunder S, Hanukoglu A, et al. Mutations in subunits of the epithelial sodium channel cause salt wasting with hyperkalaemic acidosis, pseudohypoaldosteronism type 1. Nat Genet 1996;12(3):248-53
   PubMed Web of Science ®Google Scholar
• Kerem E, Bistritzer T, Hanukoglu A, et al. Pulmonary epithelial sodium-channel dysfunction and excess airway liquid in pseudohypoaldosteronism. N Engl J Med 1999;341(3):156-62
   PubMed Web of Science ®Google Scholar
• Mall M, Grubb BR, Harkema JR, et al. Increased airway epithelial Na+ absorption produces cystic fibrosis-like lung disease in mice. Nat Med 2004;10(5):487-93
   PubMed Web of Science ®Google Scholar
• Azad AK, Rauh R, Vermeulen F, et al. Mutations in the amiloride-sensitive epithelial sodium channel in patients with cystic fibrosis-like disease. Hum Mutat 2009;30(7):1093-103
   PubMed Web of Science ®Google Scholar
• Rauh R, Diakov A, Tzschoppe A, et al. A mutation of the epithelial sodium channel associated with atypical cystic fibrosis increases channel open probability and reduces Na+ self inhibition. J Physiol (Lond) 2010;588(Pt 8):1211-25
   Google Scholar
• Mall MA. Role of the amiloride-sensitive epithelial Na+ channel in the pathogenesis and as a therapeutic target for cystic fibrosis lung disease. Exp Physiol 2009;94(2):171-4
   PubMed Web of Science ®Google Scholar
• Kunzelmann K, Schreiber R. Airway epithelial cells-Hyperabsorption in CF? Int J Biochem Cell Biol 2012;44(8):1232-5
   PubMed Web of Science ®Google Scholar
• Goralski JL, Boucher RC, Button B. Osmolytes and ion transport modulators: new strategies for airway surface rehydration. Curr Opin Pharmacol 2010;10(3):294-9
   PubMed Web of Science ®Google Scholar
• Donaldson SH, Bennett WD, Zeman KL, et al. Mucus clearance and lung function in cystic fibrosis with hypertonic saline. N Engl J Med 2006;354(3):241-50
   PubMed Web of Science ®Google Scholar
• Graeber SY, Zhou-Suckow Z, Schatterny J, et al. Hypertonic Saline is Effective in the Prevention and Treatment of Mucus Obstruction but not Airway Inflammation in Mice with Chronic Obstructive Lung Disease. Am J Respir Cell Mol Biol 2013
   Web of Science ®Google Scholar
• Baer JE, Jones CB, Spitzer SA, et al. The potassium-sparing and natriuretic activity of N-amidino-3,5-diamino-6-chloropyrazinecarboxamide hydrochloride dihydrate (amiloride hydrochloride). J Pharmacol Exp Ther 1967;157(2):472-85
   PubMed Web of Science ®Google Scholar
• Bull MB, Laragh JH. Amiloride. A potassium-sparing natriuretic agent. Circulation 1968;37(1):45-53
   PubMed Web of Science ®Google Scholar
• Bentley PJ. Amiloride: a potent inhibitor of sodium transport across the toad bladder. J Physiol (Lond) 1968;195(2):317-30
   Google Scholar
• Salako LA, Smith AJ. Effects of amiloride on active sodium transport by the isolated frog skin: evidence concerning site of action. Br J Pharmacol 1970;38(4):702-18
   PubMed Web of Science ®Google Scholar
• Canessa CM, Horisberger JD, Rossier BC. Epithelial sodium channel related to proteins involved in neurodegeneration. Nature 1993;361(6411):467-70
   PubMed Web of Science ®Google Scholar
• Kleyman TR, Cragoe EJ. Amiloride and its analogs as tools in the study of ion transport. J Membr Biol 1988;105(1):1-21
   PubMed Web of Science ®Google Scholar
• Hunt T, Atherton-Watson HC, Axford J, et al. Discovery of a novel chemotype of potent human ENaC blockers using a bioisostere approach. Part 1: quaternary amines. Bioorg Med Chem Lett 2012;22(2):929-32
   PubMed Web of Science ®Google Scholar
• Hunt T, Atherton-Watson HC, Collingwood SP, et al. Discovery of a novel chemotype of potent human ENaC blockers using a bioisostere approach. Part 2: alpha-Branched quaternary amines. Bioorg Med Chem Lett 2012;22(8):2877-9
   PubMed Web of Science ®Google Scholar
• Fronius M, Bogdan R, Althaus M, et al. Epithelial Na+ channels derived from human lung are activated by shear force. Respir Physiol Neurobiol 2010;170(1):113-19
   PubMed Web of Science ®Google Scholar
• App EM, King M, Helfesrieder R, et al. Acute and long-term amiloride inhalation in cystic fibrosis lung disease. A rational approach to cystic fibrosis therapy. Am Rev Respir Dis 1990;141(3):605-12
   PubMed Web of Science ®Google Scholar
• Knowles MR, Church NL, Waltner WE, et al. A pilot study of aerosolized amiloride for the treatment of lung disease in cystic fibrosis. N Engl J Med 1990;322(17):1189-94
   PubMed Web of Science ®Google Scholar
• Köhler D, App E, Schmitz-Schumann M, et al. Inhalation of amiloride improves the mucociliary and the cough clearance in patients with cystic fibroses. Eur J Respir Dis Suppl 1986;146:319-26
   PubMedGoogle Scholar
• Riedler J, Huttegger I. Pilotstudie zur Amiloridinhalation bei Kindern mit cystischer Fibrose. Klin Padiatr 1992;204(3):158-62
   PubMed Web of Science ®Google Scholar
• Graham A, Hasani A, Alton EW, et al. No added benefit from nebulized amiloride in patients with cystic fibrosis. Eur Respir J 1993;6(9):1243-8
   PubMed Web of Science ®Google Scholar
• Cuthbert AW. New horizons in the treatment of cystic fibrosis. Br J Pharmacol 2011;163(1):173-83
   PubMed Web of Science ®Google Scholar
• Hirsh AJ, Sabater JR, Zamurs A, et al. Evaluation of second generation amiloride analogs as therapy for cystic fibrosis lung disease. J Pharmacol Exp Ther 2004;311(3):929-38
   PubMed Web of Science ®Google Scholar
• Hofmann T, Stutts MJ, Ziersch A, et al. Effects of topically delivered benzamil and amiloride on nasal potential difference in cystic fibrosis. Am J Respir Crit Care Med 1998;157(6 Pt 1):1844-9
   PubMed Web of Science ®Google Scholar
• Rodgers HC, Knox AJ. The effect of topical benzamil and amiloride on nasal potential difference in cystic fibrosis. Eur Respir J 1999;14(3):693-6
   PubMed Web of Science ®Google Scholar
• Hirsh AJ, Molino BF, Zhang J, et al. Design, synthesis, and structure-activity relationships of novel 2-substituted pyrazinoylguanidine epithelial sodium channel blockers: drugs for cystic fibrosis and chronic bronchitis. J Med Chem 2006;49(14):4098-115
   PubMed Web of Science ®Google Scholar
• Hirsh AJ, Zhang J, Zamurs A, et al. Pharmacological properties of N-(3,5-diamino-6-chloropyrazine-2-carbonyl)-N′-4-[4-(2,3-dihydroxypropoxy)phenyl]butyl-guanidine methanesulfonate (552-02), a novel epithelial sodium channel blocker with potential clinical efficacy for cystic fibrosis lung disease. J Pharmacol Exp Ther 2008;325(1):77-88
   PubMed Web of Science ®Google Scholar
• Rogers CS, Stoltz DA, Meyerholz DK, et al. Disruption of the CFTR gene produces a model of cystic fibrosis in newborn pigs. Science 2008;321(5897):1837-41
   PubMed Web of Science ®Google Scholar
• Rogers CS, Abraham WM, Brogden KA, et al. The porcine lung as a potential model for cystic fibrosis. Am J Physiol Lung Cell Mol Physiol 2008;295(2):L240-63
   PubMed Web of Science ®Google Scholar
• Zhou Z, Treis D, Schubert SC, et al. Preventive but not late amiloride therapy reduces morbidity and mortality of lung disease in betaENaC-overexpressing mice. Am J Respir Crit Care Med 2008;178(12):1245-56
   PubMed Web of Science ®Google Scholar